The NHGRI Office of the Clinical Director manages Clinical Support Services for Genetics and Genomics in a variety of ways. 1. The Office provides extensive administrative support for medical personnel in their performance of clinical research into rare genetic diseases. This includes credentialing of health care professionals, support of their state licenses, provision of parking spaces for acute care providers, scheduling of patients and their tests, arranging contracts for clinical testing, and providing reimbursement for travel, outside medical testing, and especially genetic testing. 2. The Office also provides academic support and infrastructure for clinical investigators, including the setting of policies for the Institute, assisting in patient recruitment, handling patient, physician, and Congressional inquiries by phone, FAX, or e-mail, providing advice regarding clinical protocol writing, tracking protocols through the Institutional Review Board (IRB) approval system, managing monitoring of the Institute's clinical protocols, establishing a Data Safety and Monitoring Board and arranging its meetings twice a year, and creating and maintaining a Statistical Consultation Service for the entire Institute. The Clinical Director also supervises the administrative personnel as well as research nurses and nurse practitioners for the Institute, and schedules ward coverage. The Clinical Director provides financial and administrative supervision of the Bioethics Core and the IRB. This year the NHGRI IRB joined with the NHLBI IRB to form the Internal Medicine 1 IRB, with transfer of the data system from PTMS to IRIS. 3. The Unit on Glycosphingolipid Storage Disorders performs translational studies on Tay-Sachs and Sandhoff diseases and GM1 gangliosidosis. Using cerebral organoids from patient-derived induced pluripotent stem cells (iPSC), the Unit is testing gene therapy and small molecules to treat these fatal lysosomal storage diseases. Specifically, the Unit is using RNA expression analysis in the cerebral organoids and brain tissue to explore the earliest perturbations in brain development resulting from mutations in HEXA and HEXB. Recipient of a NISC pilot project grant, the Unit is analyzing exome sequences from a cohort of Type II GM1 gangliosidosis patients to identify variants in 1300 lysosomal-related genes as potential modifiers of disease presentation. Lastly, the Unit is phenotyping a CRISPR-generated GM1 knock out mouse that mirrors the manifestations and disease progression in patients with Type II (juvenile) GM1; this will greatly aid the lab and the field in identifying therapeutic targets for GM1 disease. 4. The Office of the Clinical Director advances clinical and translational research in the NHGRI by fostering new initiatives such as the NIH Undiagnosed Diseases Program (in collaboration with the NIH Clinical Center). This initiative, a model for Precision Medicine, provides answers to patients with mysterious conditions that have eluded diagnosis, and advances medical knowledge. The Intramural UDP is part of the Undiagnosed Diseases Network (UDN), a national consortium of 12 clinical sites, a coordinating center, sequencing center, biorepository, two model systems cores, and a metabolomics core. Over the past 10 years, the NIH UDP reviewed over 4000 medical records, evaluated over 1200 patients, and diagnosing over 200 rare and novel disorders. Two Section members sit on the UDN Working Group, and This year, Section members delivered over 20 national and international talks on the UDP, fostered expansion of the Undiagnosed Diseases Network International (UDNI) for sharing phenotypic and sequence data, and organized the 6th international UDNI meeting in Naples. The Head of the Unit on Glycosphingolipid Storage Disorders is Co-Chair of the UDN Steering Committee. 5. The NHGRI Clinical Director supports the Clinical Center by contributing to the hospital's policy making, participating in biweekly meetings of the Medical Executive Committee, and representing the Clinical Center to distinguished visitors. 6. The NHGRI OCD manages the Institute's recent initiatives regarding patient safety, protocol monitoring, event reporting, and data management. This past year, the OCD contracted for clinical database data entry support, protocol monitoring, and handling of IND correspondence with the FDA. The OCD also set policies and managed the assignment of Staff Clinicians to the status of either Assistant, Associate, or Senior Staff Clinician. The OCD verified adverse event training for the entire NHGRI clinical staff, and the Clinical Director made quarterly reports to the NHGRI Director and Scientific Director.